Attachment of 4-amino-4-deoxy-l-arabinose to phosphates or sugar hydroxyl groups of lipopolysaccharide contributes to bacterial resistance against common antibiotics. For a detailed study of antigenic properties and binding interactions, Ara4N-containing inner core ligands related to Burkholderia and Proteus LPS have been synthesized in good yields. Glycosylation at position 8 of allyl glycosides of oct-2-ulosonic acids (Ko, Kdo) has been accomplished using an N-phenyltrifluoroacetimidate 4-azido-4-deoxy-l-arabinosyl glycosyl donor followed by azide reduction and global deprotection. The β-L-Ara4N-(1→8)-α-Kdo disaccharide was further extended into the branched β-L-Ara4N-(1→8)[α-Kdo-(2→4)]-α-Kdo trisaccharide via a regioselective glycosylation of a protected triol intermediate. Synthesis of Ara4N-modified lipid A - part structure occurring in the LPS of Burkholderia, Pseudomonas and Klebsiellla strains was accomplished using the H-phosphonate approach. The stereocontrolled assembly of the phosphodiester linkage connecting glycosidic centres of two aminosugars was elaborated employing an anomeric H-phosphonate of cyclic silyl-ether protected 4-azido-4-deoxy-β-L-arabinose which was coupled to the hemiacetal of the lipid A GlcN-disaccharide backbone. Conditions for global deprotection which warrant the integrity of 'double anomeric' phosphodiester linkage were successfully developed. Introduction of thiol-terminated spacer at the synthetic ligands allows both coupling to BSA and immobilization on gold nanoparticles as well as generation of glycoarrays.

Lipopolysaccharide, carbohydrates, Kdo, lipid A, endotoxins, organic synthesis, antimicrobial activity, phosphodiesters

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8
1,8	bLArap4N	99.91	68.53	68.90	52.23	60.07
1	aXKdop	176.00	100.99	34.92	67.03	66.79	72.34	67.23	70.85
	Allyl	65.19	134.60	118.50


1H NMR data:
missing...

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

C=CCO[C@]1(C(=O)O)C[C@@H](O)[C@@H](O)[C@@H]([C@H](O)CO[C@H]2OC[C@H](N)[C@H](O)[C@H]2O)O1

409.388 g/mol (C₁₆H₂₇NO₁₁)